Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications

ABSTRACT

Introduction

miRNA-derivative clinical nucleotide drugs (mdCNDs) effectively treat several diseases, with numerous undergoing clinical trials. In early-stage trials in disease therapeutics, such as malignant pleural mesothelioma and hepatic virus C infection, mdCND’s therapeutic potency is undeniably good for effectiveness and safety.

Areas covered

Fifteen mdCNDs undergoing clinical trials are introduced in this review. MiRNA modifications methods have been summarized, including phosphorothioate, cholesterol, locked nucleic acid, 2ʹ-O-methyl, N,N-diethyl-4-(4-nitronaphthalen1-ylazo)-phenylamine modifications, and many more. Moreover, delivery systems, including self-assembled, inorganic ions nanoparticles, exosomes, and lipid-based nanosystems for mdCNDs targeted delivery, are presented. Among that, EnGeneIC, N-Acetylgalactosamine, liposomal nanoparticles, and cholesterol-conjugated for mdCNDs delivery are currently undergoing clinical trials. The pH, light, temperature, redox-responsive, enzyme, and specific-substance modes to trigger the release of miRNAs to target sites on-demand and the prospects of mdCNDs are discussed in this review.

Expert opinion

mdNCDs are one type of promising clinical drugs, however, it is still in the infancy. During the development process, it is imperative to advance in modifying miRNAs, especially at the 5′-end, to enhance targetability and stability against nucleases, develop a stimuli-responsive mode to control the release of mdCNDs to tissue cell-type-specific sites.

Graphical abstract

KEYWORDS:

• MiRNA-derivative nucleotide drugs
• application
• modifications
• delivery systems
• stimuli-responsive system

Article highlights

• Summary of miRNA-derivative clinical nucleotide drugs (mdCNDs) in clinical trials

• Modifications of miRNA-derivative clinical nucleotide drugs have been summarized

• Four delivery systems used for miRNA-derivative clinical nucleotide drugs treatment

• Summary of challenges of miRNA-derivative clinical nucleotide drugs

• Six stimuli-responsive systems to trigger the release of mdCNDs are discussed

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was supported by HeBei Provincical key research and development program (CN) [21372801D], the National Natural Science Foundation of China [No.31871875], and the 2115 Talent Development Program of China Agricultural University [No. 00109016].